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Tom Rapoport, an HHMI investigator at Harvard Medical School, has shown how defects in the membranes of the endoplasmic reticulum can lead to diseases.
From birth defects to neural degeneration, when a cell can't control its membranes, the effects are severe. Studying the diseases that result from disorganized membranes has illuminated basic biochemical processes that keep membranes at equilibrium.

The outer surface of a cell is a membrane, and membranes also divide a cell's contents into discrete areas. Like a house with rooms dedicated to different purposes—eating, sleeping, cooking—a cell has compartments for different processes—building proteins, storing chemical messengers, generating energy. The walls of the cell's rooms are membranes.
When material in a cell needs to move from one spot to another, it moves in a vesicle, a membrane-enclosed sac. Randy Schekman, an HHMI investigator at the University of California, Berkeley, focuses on vesicles that transport newly made proteins out of the endoplasmic reticulum (ER), which is itself a maze of membranes. The ER is involved in synthesizing, folding, and transporting proteins produced by the ribosome. But not all proteins are destined to leave the organelle. The vesicle-creation machinery is selective, picking off the ER assembly line only proteins that display certain chemical signals—like the zip codes a post office needs to ship packages.
“There has to be a way of ensuring that only a restricted set of proteins are transported from one place to the next,” he says. “Otherwise everything would blend.” [Cells have a system for sending wayward proteins from the Golgi back to the ER. See Web Extra “Return to Sender.”]
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Return to Sender
Studying the structures of proteins involved in membrane fission and fusion...

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Photo: Leah Fasten
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